O-GlcNAc modification of transcription factors, glucose sensing and glucotoxicity.
Regulation of proteins by O-GlcNAc modification is becoming a major area of research. This reversible modification depends on glucose concentrations and, therefore, constitutes a powerful mechanism to regulate protein activities according to glucose availability. Its importance in glucose-dependent gene transcription is underlined by its role in pancreatic insulin biosynthesis (through PDX-1 and NeuroD1 O-GlcNAc modifications) and leptin synthesis in adipose tissue (through Sp1 O-GlcNAc modification). Moreover, in chronic hyperglycaemia, O-GlcNAc modifications of Sp1, p53 and NFkappaB participate in glucotoxicity, resulting in cardiovascular and renal alterations. The recent discovery by two independent groups that FoxO1 is regulated by O-GlcNAc modification provides a potential mechanism by which hyperglycaemia promotes gluconeogenesis and worsening of glucose intolerance, opening new research perspectives in the field.
Issad
Tarik
T
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France. tarik.issad@inserm.fr
Kuo
Meishiue
M
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000009:adverse effects* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
D014157:Transcription Factors; D005947:Glucose; D000117:Acetylglucosamine